The cytotoxic action of adriamycin and cyclophosphamide on tumor cells in vitro and in vivo

The ability of Adriamycin (ADR) to kill tumor cells were studied using two transplantable murine tumors adapted for growth in tissue culture. Cells were treated either in vivo as subcutaneous (SC) tumors or lung colonies up to 2 mm in diameter or in vitro. ADR in contact with cells in vitro for one hour readily killed cells from both CBSAF and WHFIB tumors. Cells plated from tumors were more resistant in vitro than cells kept in culture. The D₀'s were 0.17 and 0.1 gm/ml, respectively. The resistant tail in WHFIB at 10^?2 survival was not inherited by surviving cells. In log phase the D was reduced. However, in vivo an IP or IV dose of 18 μ/ml ADR to mice bearing CBSAF tumors produced a surviving fraction as high as 0.64 for SC tumors and 0.3 for lung colonies.Hypoxic tumor cells in vitro are more resistant than aerobic ones; there may also be a tumor size effect because lung colony cells treated in vitro has a sensitivity intermediate between SC tumors and cultured cells; but even both factors together cannot explain the lack of effect in vivo relative to in vitro. Preliminary studies with cyclophosphamide suggested that it, in contrast to ADR, was highly effective in killing tumor cells both in SC tumors and in lung colonies.